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a white precipitate, which was filtered and dried in vacuo at
room temperature. The formed dicarboxylic acids 8a–d
were suspended in toluene (10 mL) and heated at reflux
for 2 h. The solvent was removed in vacuo, affording the
pure product.
4.3.10.4.
rac-2-Acetamido-3-(benzo[b]thiophen-3-yl)-
propanoic acid rac-9d. Yield = 85%; mp 154 °C from tol-
uene (153 °C from benzene–petroleum ether14); HRMS:
M+ found (M+ calculated for C13H13NO3S): 263.06180
(263.06161); MS: m/z (%) = 263 (22.57, M), 206 (5.38),
205 (9.72), 204 (80.60), 195 (3.92), 191 (4.19), 181 (4.36),
176 (4.69), 175 (4.37), 167 (5.28), 165 (4.75), 163 (4.22),
162 (7.43), 161 (4.47), 160 (4.29), 153 (7.79), 151 (6.44),
149 (10.58), 148 (10.67), 147 (100.00), 141 (4.07), 139
(4.49), 137 (7.13), 136 (4.06), 135 (4.72), 134 (4.88), 127
(4.87), 126 (4.02), 125 (10.91), 124 (4.15), 123 (8.97), 121
(4.98), 115 (7.52), 113 (5.17), 112 (4.43), 111 (16.32), 110
(5.23), 109 (11.35), 107 (4.75), 103 (4.43), 99 (6.05); 1H
NMR (DMSO-d6): d = 1.75 (s, 3H), 3.36–3.40 (m, 2H),
4.38–4.41 (m, 1H), 7.32–7.35 (m, 2H), 7.39 (s, 1H), 7.82
(d, 1H), 7.91 (d, 1H); 13C NMR (DMSO-d6): d = 22.7,
30.9, 53.9, 121.7, 122.6, 122.8, 123.8, 123.9, 133.6, 139.2,
139.3, 168.7, 175.5.
4.3.10.1. rac-2-Acetamido-3-(benzofuran-2-yl)propanoic
acid rac-9a. Yield = 81%; mp 115 °C from ethyl ace-
tate–hexane; HRMS: M+ found (M+ calculated for
C13H13NO4): 247.08482 (247.08446); MS: m/z (%) = 248
(2.12, M+1), 247 (14.31, M), 229 (0.51), 216 (0.63), 204
(1.88), 201 (0.67), 190 (1.08), 189 (11.04), 188 (100.00),
187 (0.74), 171 (2.41), 170 (0.56), 167 (0.55), 161 (0.91),
160 (7.32), 159 (2.84), 158 (0.63), 149 (1.02), 147 (2.51),
146 (5.42), 145 (0.62), 144 (2.93), 143 (0.60), 142 (1.30),
134 (0.74), 133 (1.42), 132 (7.61), 131 (52.11), 130 (1.02),
129 (0.46), 118 (1.63), 116 (0.54), 115 (2.74), 114 (0.46),
105 (1.22), 104 (0.63), 103 (3.11), 102 (2.04), 101 (0.55),
1
97.1 (0.60); H NMR (DMSO-d6): d = 1.80 (s, 1H), 3.05–
4.3.11. Synthesis of rac-propyl 2-acetamido-3-(hetero-
aryl)propanoates rac-10a–d. Into a solution of carbonyl-
diimidazole (90 mg, 0.55 mmol) and rac-2-acetamido-
3-(heteroaryl)propanoic acid rac-9a–d (0.5 mmol) in
anhydrous THF (2.5 mL), 1-propanol (45 mg, 56 lL, 0.75
mmol) was added in one portion at room temperature.
After the reaction was complete (checked by TLC), the sol-
vent was distilled off in vacuo and the crude product was
purified with column chromatography on silica gel using
as eluent dichloromethane–acetone 90:10 (v/v). Methyl,
ethyl and butyl 2-acetamido-3-(heteroaryl)propanoates
were prepared in the same manner.
3.27 (m, 2H), 4.43–4.49 (m, 1H), 6.60 (s, 1H), 7.15–7.23
(m, 2H), 7.47 (d, 1H), 7.53 (d, 1H), 8.08 (d, 1H, NH);
13C NMR (DMSO-d6): d = 22.5, 30.7, 51.6, 103.4, 110.6,
120.4, 122.5, 123.3, 128.5, 154.0, 156.0, 169.0, 172.9.
4.3.10.2.
rac-2-Acetamido-3-(benzo[b]thiophen-2-yl)-
propanoic acid rac-9b. Yield = 83%; mp 208 °C from
ethyl acetate–hexane (decomp.); HRMS: M+ found (M+
calculated for C13H13NO3S): 263.06191 (263.06161); MS:
m/z (%) = 263 (20.59. M), 206 (6.23), 205 (14.06), 204
(97.76), 187 (3.79), 176 (6.23), 163 (2.85), 162 (7.50), 161
(4.60), 160 (4.30), 154 (2.51), 153 (17.42), 151 (5.57), 150
(4.97), 149 (9.39), 148 (13.28), 147 (100.00), 136 (7.52),
135 (2.57), 134 (8.23), 121 (4.74), 116 (2.67), 115 (11.09),
108 (5.79), 107 (19.76), 106 (14.60), 105 (7.02), 104 (2.54),
103 (7.03), 102 (3.71), 91 (18.08), 90 (2.56); 1H NMR
(DMSO-d6): d = 1.84 (s, 3H), 3.18–3.39 (m, 2H), 4.47–
4.32 (m, 1H), 7.20 (s, 1H), 7.26–7.35 (m, 2H), 7.75 (d,
1H), 7.88 (d, 1H), 8.33 (d, 1H, NH); 13C NMR (DMSO-
d6): d = 22.5, 32.0, 53.2, 122.1, 122.7, 123.0, 123.8, 124.2,
139.0, 139.5, 141.0, 169.4, 172.5.
4.3.11.1. rac-Propyl 2-acetamido-3-(benzofuran-2-yl)-
propanoate rac-10a. Yield = 89%; semisolid, HRMS:
M+ found (M+ calculated for C16H19NO4): 289.13163
(289.13141); MS: m/z (%) = 291 (1.8, M+2), 290 (18,
M+1), 289 (100, M), 288 (17), 287 (12), 284 (11.5), 279
(20.5), 278 (20.5), 268 (11.3), 264 (20.8), 258 (27.1), 257
(15.2), 248 (58.4), 242 (17.3), 231 (18.5), 229 (12.4), 225
(12.7), 215 (12.3), 212 (13.6), 209 (14.9), 193 (22.1), 176
1
(12.2), 159 (20.1), 129 (14.6); H NMR (CDCl3): d = 0.92
(t, 3H), 1.60–1.74 (m, 2H), 1.99 (s, 3H), 3.33 (d, 2H),
4.05–4.18 (m, 2H), 4.92–4.98 (m, 1H), 6.47 (1H, NH),
6.49 (s,1H), 7.16–7.26 (m, 2H), 7.39 (d, 1H), 7.49 (d, 1H);
13C NMR (CDCl3): d = 10.3, 21.8, 23.0, 31.0, 51.2, 67.4,
104.9, 110.8, 120.6, 122.7, 123.8, 128.3, 153.5, 154.9,
170.0, 171.2.
4.3.10.3. rac-2-Acetamido-3-(benzofuran-3-yl)propanoic
acid rac-9c. Yield = 86%; mp 156 °C from ethanol–water
(155–156 °C from water21); HRMS: M+ found (M+ calcu-
lated for C13H13NO4): 247.08531 (247.08446); MS: m/z
(%) = 249 (0.49, M+2), 248 (4.27, M+1), 247 (29.44, M),
232 (0.25), 229 (0.87), 216 (0.79), 206 (0.26), 205 (0.72),
204 (3.99), 203 (1.60), 202 (0.55), 201 (0.65), 190 (1.03),
189 (10.04), 188 (100.00), 187 (3.50), 186 (0.54), 185
(0.37), 172 (0.39), 171 (2.19), 170 (0.24), 162 (0.32), 161
(1.07), 160 (8.72), 159 (4.34), 158 (1.60), 149 (0.28), 148
(0.38), 147 (3.17), 146 (25.27), 145 (2.05), 144 (6.47), 143
(0.37), 142 (0.55), 134 (0.52), 133 (1.23), 132 (8.96), 131
(79.93), 130 (1.62), 121 (0.74), 119 (0.31), 118 (2.73), 117
(0.45), 116 (0.71), 115 (4.11), 114 (0.39), 105 (1.18), 104
4.3.11.2. rac-Propyl 2-acetamido-3-(benzo[b]-thiophen-2-
yl)propanoate rac-10b. Yield = 88%; semisolid, HRMS:
M+ found (M+ calculated for C16H19NO3S): 305.10796
(305.10856); MS: m/z (%) = 307 (9.8, M+2), 306 (23.1,
M+1), 305 (100, M), 304 (32.9), 303 (31.6), 302 (13.9),
301 (14.0), 300 (35.6), 290 (64.1), 289 (69.6), 288 (33.4),
287 (36.8), 286 (39.1), 285 (16.2), 275 (20.1), 271 (17.4),
270 (70.4), 260 (16.6), 257 (15.4), 256 (26.7), 247 (16.6),
225 (24.4), 219 (15.2), 213 (23.5), 201 (8.9), 185 (11.3),
1
(1.09), 103 (7.21), 102 (1.78), 101 (0.24), 91.1 (0.49); H
1
NMR (DMSO-d6): d = 1.86 (s, 3H), 3.01–3.21 (m, 2H),
4.35–4.61 (m, 1H), 7.30–7.39 (m, 2H), 7.60 (d, 2H), 7.71
(d, 1H), 7.81 (s, 1H), 8.33 (d, 1H, NH); 13C NMR
(DMSO-d6): d = 22.3, 25.3, 51.8, 111.2, 116.0, 119.6,
122.5, 124.2, 127.7, 142.9, 154.4, 169.3, 173.9.
170(6.7), 144 (2.3), 127 (6.8); H NMR(300 MHz, CDCl3):
d = 0.94 (t, 3H), 1.63–1.74 (m, 2H), 2.03 (s, 3H), 3.38–3.52
(m, 2H), 4.12 (t, 2H), 4.92–4.98 (m, 1H), 6.43 (1H, NH),
7.01 (s, 1H), 7.25–7.35 (m, 2H), 7.69 (d, 1H), 7.76 (d,
1H); 13C NMR (75 MHz, CDCl3): d = 10.3, 21.8, 23.1,